Trial of Bendamustine And Rituximab for Patients With Previously Untreated Extranodal Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma

Multicentric, Non-Randomized Phase 2 Trial of Bendamustine And Rituximab for Patients With Previously Untreated Extranodal Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma

The aim of the study is to assess the therapeutic activity and safety of the combination of Bendamustine and Rituximab in MALT lymphomas.

Primary endpoint:

• Event-free-survival (EFS) (failure or death from any cause) for all patients.

Secondary endpoints:

• Complete and partial remission rates for all patients
• Response duration (time to relapse or progression) for responder patients
• Progression-free-survival (PFS) (disease progression or death from lymphoma: for all patients
• Overall survival for all patients
• Acute and long-term toxicity

Inclusion Criteria:

1. Histologically proven diagnosis of CD20-positive marginal zone B-cell lymphoma of MALT type arisen at any extranodal site (WHO classification)

2. Any stage (Ann Arbor I-IV)

3. The novo disease en any extranodal site. For primary gastric or cutaneous lymphoma, local/specific previous treatment is accepted, just following the below criteria:

   1. Cutaneous lymphoma: recurrent lymphoma after local therapy
   2. Gastric lymphoma:

   b1. H. pylori-negative cases, either de novo (non pre-treated) or at relapse following local therapy (i.e., surgery, radiotherapy or antibiotics).

   b2. H. pylori-positive cases at diagnosis, who failed antibiotic therapy, including patients with: clinical (endoscopic) and histological evidence of disease progression at any time post H. pylori eradication; stable disease with persistent lymphoma at 1 year post H. pylori eradication; relapse (without H. pylori re-infection), after a remission; patients who failed either first line antibiotics or further local treatment (surgery or radiotherapy)

4. No evidence of histologic transformation to a high grade lymphoma

5. Measurable or evaluable disease

6. Age >18 and <85

7. ECOG performance status 0-2

8. Life expectancy of at least 1 year

9. Written informed consent given according to national/local regulations

Exclusion Criteria:

1. Prior chemotherapy or prior immunotherapy with any anti-CD20 monoclonal antibody
2. Prior radiotherapy in the last 6 weeks
3. Corticosteroids during the last 28 days, unless prednisone chronically administered at a dose <20 mg/day for indications other than lymphoma or lymphoma-related symptoms
4. Major impairment of renal function (serum creatinine > 2,5 x upper normal) or liver function (ASAT/ALAT <2,5 x upper normal, total bilirubin <2,5x upper normal), unless due to lymphoma involvement.
5. Impairment of bone marrow function (WBC <3.0x109/L, ANC <1.5x109/L, PLT <100x109/L), unless due to lymphoma involvement
6. Evidence of clinically significant cardiac, neurological or metabolic disease, unless due to lymphoma involvement
7. Evidence of symptomatic central nervous system (CNS) disease
8. Active HBV and/or HCV infection
9. Known HIV infection
10. Prior diagnosis of neoplasm within 5 years, except cervical intraepithelial neoplasia type 1 (CIN1) or localized non-melanomatous skin cancer
11. Any psychiatric disease potentially hampering compliance with the study protocol and follow-up schedule
12. Potential to attend regular visits to the hospital, on an outpatient regimen
13. Hypersensibility to any compound of the study medication.
14. Non appropriate contraceptive method in women of childbearing potential or men
15. Treatment with any drug under research within 30 days previous to start the study medication.